Articular cartilage is a distinct tissue because it is aneural, avascular, and has a very limited capability for self-repair (Buckwalter et al., 1987, Calcif Tissue Int., 41:228-36; Hunziker et al., 1996, J Bone Joint Surg Am., 78:721-33). Traumatic and mechanical injuries, whether full or partial thickness, cannot spontaneously heal and degeneration usually prevails over regeneration and osteoarthritis develops. On the molecular level, osteoarthritis develops as a consequence of the sequential destruction of the articular cartilage surface, which includes the release of cartilage matrix molecules, such as collagens and aggrecan from the articular surface (Dodge et al., 1989, J Clin Invest., 83:647-61; Sandy et al., 1984, Arthritis Rheum., 27:388-97). Although damaged cartilage has a very limited self-repair capability there is evidence that remaining articular chondrocytes do attempt to compensate for matrix degradation by up-regulating matrix molecules production (Lippiello et al., 1977, J Clin Invest., 59:593-600; Eyre et al., 1980, Biochem J., 188:823-37). Ultimately, this up-regulation in chondrocyte metabolic activity and cartilage matrix production is insufficient to compensate for the catabolic events and the continued destruction of cartilage is exacerbated by the limited ability of adult chondrocytes to divide and replace lost chondrocytes. One of the major reasons for this “losing battle” is the fact that cartilage as a non-vascularized tissue, does not have access to a source of stem cells, such as the mesenchymal stem cells of bone marrow (Owen, 1988, J Cell Sci Suppl., 10:63-76; Caplan et al., 1997, Clin Orthop., 342:254-69), nor does articular cartilage have a source of pre-chondrogenic cells, as is found in the periosteum (Nakahara et al., 1990, Clin Orthop., 259:223-32; O'Driscoll, 1999, Clin Orthop., 367 Suppl:S186-203; Brittberg, 1999, Clin Orthop., 367 Suppl:S147-55). Short of completely replacing the articular cartilage, methods directed at the repair of cartilage must overcome these inherent self-repair deficiencies either by promoting increased chondrogenesis of cells within the articular cartilage or by increasing the number of chondrogenic cells at the injured area. Therapies directed to treat damaged cartilage are very limited and are divided into two general approaches. The first approach is non-surgical treatments such as analgesics, non-steroidal anti inflammatory drugs, and even localized intraarticular injections of steroids. This treatment option is often combined with modification of weight bearing and physical therapy aimed at pain relief, muscle strengthening, and the preservation of range of motion. All the above-mentioned are aimed at pain relief and none have been shown to affect the natural disease progression or the cause of the problem. Another non surgical technique used to enhance healing, is the local application of growth factors and oral supplements such as TGF-B, hyaluronic acid and chondroitin sulphate in an effort to change the environment so it will be favorable for healing (Maniwa et al., 2001, Acta Orthop Scand., 72:299-303). The second general approach is surgical and it is divided into three main categories: treatments that aim at promoting self-healing doing that by changing the local environment by allowing cells originating in adjacent tissue (bone marrow) to migrate, adhere, multiply and repair the injured site. This is done by penetrating the sub-chondral bone, for example, the arthroscopic shaving technique, sub-chondral drilling and sub-chondral micro-fractures (Convery et al., 1994, Contemp Orthop., 28:101-7; Blevins et al., 1998, Orthopedics., 21:761-7; Sledge, 2001, Clin Sports Med., 20:365-77). Other surgical treatments include osteochondral grafting, either allogeneic or autogeneic, in an effort to reconstruct the defect area (Meyers et al., 1989, J Bone Joint Surg Am., 71:704-13; Buckwalter et al., 1994, J Am Acad Orthop Surg.m 2:192-201; Hangody et al., 2001, Foot Ankle Int., 22:552-8) by using healthy osteochondral implants. The third surgical approach is based on tissue engineering, the end goal of which is regenerative fabrication of tissues by manipulating cells, scaffolds and signals in-vitro (Caplan, 2000, Tissue Eng., 6:1-8). Current applications of tissue engineering to articular cartilage have focused on manipulating cartilage-forming cells, committed chondrocytes (Itay et al., 1987, Clin Orthop., 220:284-303) or osteochondral progenitor cells (Yoo et al., 1998, J Bone Joint Surg Am., 80:1745-57) as a source for the tissue regenerated. One of the cornerstones/obstacles in implementing this technology is being able to direct the cells or tissue, engineered in vitro, to the precise in vivo site were repair is needed. Research focused on numerous delivery vehicles onto which the cells are loaded is taking place worldwide (Brun et al., 1999, J Biomed Mater Res., 46:337-46; Ochi et al., 2001, Artif Organs., 25:172-9) and techniques in which cells are injected into surgically constructed pockets have been published (Brittberg et al., 1994, N Engl J. Med., 331:889-95).
Efforts in tissue engineering and restorative surgery would be improved by advances in cell targeting technology.